Elevated expression of osteopontin may be related to adipose tissue macrophage accumulation and liver steatosis in morbid obesity.
OBJECTIVE
Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis.


METHODS
OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells.


RESULTS
Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery-induced weight loss induced a strong increase in circulating OPN.


CONCLUSIONS
The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury.
Bertola
Adeline
A
Institut National de la Santé et de la Recherche Médicale, U895, Team 8, Hepatic Complications in Obesity, Nice, France.
Deveaux
Vanessa
V
Bonnafous
Stéphanie
S
Rousseau
Déborah
D
Anty
Rodolphe
R
Wakkach
Abdelilah
A
Dahman
Moncef
M
Tordjman
Joan
J
Clément
Karine
K
McQuaid
Siobhán E
SE
Frayn
Keith N
KN
Huet
Pierre-Michel
PM
Gugenheim
Jean
J
Lotersztajn
Sophie
S
Le Marchand-Brustel
Yannick
Y
Tran
Albert
A
Gual
Philippe
P
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000494:pharmacology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D019301:Oleic Acid